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Role of ephrin-A1 in lung metastasis

Research Project

Project/Area Number 25870760
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General medical chemistry
Respiratory surgery
Research InstitutionTokyo Women's Medical University

Principal Investigator

IEGUCHI Katsuaki  東京女子医科大学, 医学部, 助教 (90586348)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords転移 / Eph / ephrin / ADAM / がん
Outline of Final Research Achievements

It has been reported that overexpression of ephrin-A1 is positively correlated with prognosis in various cancers such as hepatocellular carcinoma. However, the detailed function remains unclear. Therefore, I focused on metastasis that get worse their prognosis in cancer patients and analyzed functions of ephrin-A1 in lung metastasis. I found that ADAM12 identified as a proteinase against ephrin-A1, cleaved ephrin-A1 in primary tumors, and the the serum level is increased. Activated EphA2 by cleaved ephrin-A1 is immediately endocytosed and undergone proteolysis and therby localization of VE-cadherin at the plasma membrane is lost. As a result of destabilization of EphA2 and VE-cadherin at the plasma membrane in lung vascular endothelial cells leads to hyper-permeability and enhances lung metastasis. A neutralizing antibody against ephrin-A1 is effective for lung metastasis. I would like to develop anti-ephrin-A1 therapeutic drugs.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (12 results)

All 2015 2014 2013 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (3 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Human serum amyloid A3 (SAA3) protein, expressed as a fusion protein with SAA2, binds the oxidized low density lipoprotein receptor.2015

    • Author(s)
      Tomita T, Ieguchi K, Sawamura T, Maru Y
    • Journal Title

      PLoS One

      Volume: 10(3) Issue: 3 Pages: e0118835-e0118835

    • DOI

      10.1371/journal.pone.0118835

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] LINGO-1 Protein Interacts with the p75 Neurotrophin Receptor in Intracellular Membrane Compartments2015

    • Author(s)
      Meabon JS, De Laat R, Ieguchi K, Wiley JC, Hudson MP, Bothwell M
    • Journal Title

      J Biol Chem

      Volume: 290(15) Issue: 15 Pages: 9511-20

    • DOI

      10.1074/jbc.m114.608018

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ZFC3H1, a Zinc Finger Protein, Modulates IL-8 Transcription by Binding with Celastramycin A, a Potential Immune Suppressor2014

    • Author(s)
      Tomita T, Ieguchi K, Coin F, Kato Y, Kikuchi H, Oshima Y, Kurata S, Maru Y
    • Journal Title

      PLoS One

      Volume: 30 Issue: 9 Pages: e108957-e108957

    • DOI

      10.1371/journal.pone.0108957

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] ADAM12-cleaved ephrin-A1 contributes to lung metastasis.2014

    • Author(s)
      Ieguchi K, Tomita T, Omori T, Komatsu A, Deguchi A, Masuda J, Duffy SL, Coulthard MG, Boyd A, Maru Y.
    • Journal Title

      Oncogene

      Volume: 未定 Issue: 17 Pages: 2179-90

    • DOI

      10.1038/onc.2013.180

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] An integrin binding-defective mutant of insulin-like growth factor-1 (R36E/R37E IGF1) acts as a dominant-negative antagonist of the IGF1 receptor (IGF1R) and suppresses tumorigenesis but still binds to IGF1R2013

    • Author(s)
      Fujita M, Ieguchi K, Cedano-Prieto DM, Fong A, Wilkerson C, Chen JQ, Wu M, Lo SH, Cheung AT, Wilson MD, Cardiff RD, Borowsky AD, Takada YK, Takada Y
    • Journal Title

      Journal of Biological Chemistry

      Volume: 288 Issue: 27 Pages: 19593-19603

    • DOI

      10.1074/jbc.m113.470872

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ephrin-A1 expression induced by S100A8 is mediated by the toll-like receptor 42013

    • Author(s)
      Ieguchi K, Omori T, Komatsu A, Tomita T, Deguchi A, Maru Y
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 440(4) Issue: 4 Pages: 623-629

    • DOI

      10.1016/j.bbrc.2013.09.119

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Role of the sympathetic nervous system in lung metastasis2015

    • Author(s)
      Ieguchi K, Maru Y
    • Organizer
      2nd International symposium 2015 “Neuro-Vascular wiring”
    • Place of Presentation
      関西セミナーハウス(京都府・左京区)
    • Year and Date
      2015-01-18 – 2015-01-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] Breakdown of the Eph/ephrin system in vascular endothelial cells causes lung metastasis2014

    • Author(s)
      Ieguchi K, Tomita , Maru Y
    • Organizer
      The 18th International Vascular Biology Meeting
    • Place of Presentation
      京都市勧業館みやこめっせ(京都府・左京区)
    • Year and Date
      2014-04-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] ADAM12-cleaved ephrin-A1 contributes to lung metastasis2013

    • Author(s)
      Ieguchi Katsuaki, Tomita Takeshi, Yoshiro Maru
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Book] 血液内科2014

    • Author(s)
      家口勝昭、丸義朗
    • Total Pages
      7
    • Publisher
      科学評論社
    • Related Report
      2014 Annual Research Report
  • [Remarks] 東京女子医科大学 研究業績データベース

    • URL

      http://gyoseki.twmu.ac.jp/twmhp/KgApp?kyoinId=ymdmgiykggi

    • Related Report
      2013 Research-status Report
  • [Remarks] 東京女子医科大学 薬理学教室

    • URL

      http://www.twmu.ac.jp/Basic/yakuri/index.html

    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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